Regulation of apoptosis by chemotactic human ribosomal protein S19 mutant protein.

我们计划在小鼠体内发现核糖体蛋白S19二聚体(RPS19)二聚体的生物学效应，该载体带有Q137N突变型RPS19基因。初步建立了Q137N突变体-小鼠NIH3T3克隆，获得了抗锰(II)诱导的细胞凋亡。由此，我们怀疑通过Rp S19二聚体诱导的C5a受体(C5aR)介导的途径来调节细胞凋亡的能力，并向Journal报道。我们开始建立小鼠ES细胞克隆，以建立小鼠模型。同时，我们进行了Western-blotting分析，以检测更详细的C5aR途径，特别是PI3-K/Akt和ERK途径。我们发现了以下结果。(1)细胞凋亡过程中，Akt和ERK的磷酸化水平降低。(2)Q137N突变克隆在细胞凋亡过程中仍能维持Akt的磷酸化。(3)RPS19二聚体克服了Q137N突变克隆对细胞凋亡的获得性抵抗。这些结果表明，RPS19二聚体通过改变C5aR上的PI3-K/Akt和ERK信号通路在细胞凋亡中发挥重要作用。现在，我们有了一个在体外发现调节分子的最终计划。我们还对制作老鼠模型感兴趣。

We had a plan to find a biological effect of ribosomal protein S19 (RP S19) dimer in mouse which had an special vector with Q137N mutant RP S19 cDNA. Preliminary, established Q137N mutant-mouse NIH3T3 clones acquired to resistant apoptosis by manganese(II). From this, we suspected the ability to regulate apoptosis by RP S19 dimer-induced C5a receptor (C5aR)-mediated pathway, and reported to Joural. We started to establish mouse ES cell clones to make a mouse model. At the same time, we performed western-blotting analysis to detect a more detail mechanism about C5aR-mediated pathway, especially PI3-K/Akt and ERK pathway. We found following results. (1) Phosphorylated Akt and ERK were decreased during apoptosis. (2) Phosphorylated Akt was maintained during apoptosis in Q137N-mutant clones. (3) RP S19 dimer overcame the acquired resistance to apoptosis in Q137N mutant-clones. From these results, we strongly suggest that RP S19 dimer plays an important role in apoptosis through changing PI3-K/Akt and ERK pathway on C5aR. Now we have a final plan in vitro to discover a regulation molecule. We also still interested in making a mouse model.